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Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)

Sponsor
Alnylam Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05103332
Collaborator
(none)
800
Enrollment
94
Locations
6
Arms
31.8
Anticipated Duration (Months)
8.5
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of zilebesiran on systolic and diastolic blood pressure and to characterize the pharmacodynamic (PD) effects and safety of zilebesiran as add-on therapy.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
800 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Zilebesiran Used as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication
Actual Study Start Date :
Nov 5, 2021
Anticipated Primary Completion Date :
Apr 1, 2023
Anticipated Study Completion Date :
Jul 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Zilebesiran (Add-on to Olmesartan)

Following a run-in on olmesartan, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to olmesartan. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.

Drug: Olmesartan
Olmesartan administered orally

Drug: Zilebesiran
Zilebesiran administered by SC injection
Other Names:
  • ALN-AGT01

    		•
    Experimental: Placebo (Add-on to Olmesartan)

    Following a run-in on olmesartan, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to olmesartan. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.

    Drug: Olmesartan
    Olmesartan administered orally

    Drug: Placebo
    Placebo administered by subcutaneous (SC) injection

    Drug: Zilebesiran
    Zilebesiran administered by SC injection
    Other Names:
  • ALN-AGT01

    		•
    Experimental: Zilebesiran (Add-on to Amlodipine)

    Following a run-in on amlodipine, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to amlodipine. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.

    Drug: Amlodipine
    Amlodipine administered orally

    Drug: Zilebesiran
    Zilebesiran administered by SC injection
    Other Names:
  • ALN-AGT01

    		•
    Placebo Comparator: Placebo (Add-on to Amlodipine)

    Following a run-in on amlodipine, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to amlodipine. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.

    Drug: Amlodipine
    Amlodipine administered orally

    Drug: Placebo
    Placebo administered by subcutaneous (SC) injection

    Drug: Zilebesiran
    Zilebesiran administered by SC injection
    Other Names:
  • ALN-AGT01

    		•
    Placebo Comparator: Zilebesiran (Add-on to Indapamide)

    Following a run-in on indapamide, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to indapamide. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.

    Drug: Indapamide
    Indapamide administered orally

    Drug: Zilebesiran
    Zilebesiran administered by SC injection
    Other Names:
  • ALN-AGT01

    		•
    Placebo Comparator: Placebo (Add-on to Indapamide)

    Following a run-in on indapamide, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to indapamide. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period.

    Drug: Indapamide
    Indapamide administered orally

    Drug: Placebo
    Placebo administered by subcutaneous (SC) injection

    Drug: Zilebesiran
    Zilebesiran administered by SC injection
    Other Names:
  • ALN-AGT01

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change from Baseline at Month 3 in 24-Hour Mean Systolic Blood Pressure (SBP) Assessed by Ambulatory Blood Pressure Monitoring (ABPM) [Baseline and Month 3]

    Secondary Outcome Measures

    1. Change from Baseline at Month 3 in Office SBP [Baseline and Month 3]

    2. Time-adjusted Change from Baseline through Month 6 in Office SBP 24-hour Mean SBP, Assessed by ABPM [Baseline through Month 6]

    3. Proportion of Patients with 24-hour Mean SBP Assessed by ABPM <130 mmHg and/or Reduction from Baseline ≥ 20 mmHg without Escape Antihypertensive Medication at Month 6 [Baseline and Month 6]

    4. Change in 24-hour Mean SBP and DBP, Assessed by ABPM [Baseline and Month 6]

    5. Change in Office SBP and DBP [Baseline and Month 6]

    6. Change in Daytime and Nighttime Mean SBP and DBP, Assessed by ABPM [Baseline and Month 6]

      Daytime is defined as 6 am to 9:59 pm and nighttime is defined as 10 pm to 5:59 am.

    7. Change from Baseline in Serum Angiotensinogen (AGT) [Baseline through Month 6]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Office SBP at Screening as follows:

    1. ≥155 mmHg and ≤180 mmHg for patients with untreated hypertension

    2. ≥145 mmHg and ≤180 mmHg for patients on antihypertensive medications

    • 24-hour mean SBP >130 mmHg and ≤160 mmHg by ABPM after at least 4 weeks of run-in on protocol-specified background antihypertensive medication
    Exclusion Criteria:

    • Secondary hypertension, orthostatic hypotension

    • Elevated potassium >5 mEq/L

    • Estimated glomerular filtration rate (eGFR) of ≤30 mL/min/1.73m^2

    • Received an investigational agent within the last 30 days

    • Type 1 diabetes mellitus, poorly controlled Type 2 diabetes mellitus, newly diagnosed Type 2 diabetes mellitus

    • History of any cardiovascular event within 6 months prior to randomization

    • History of intolerance to SC injection(s)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Trial Site Birmingham Alabama United States 35211
    2 Clinical Trial Site Mesa Arizona United States 85213
    3 Clinical Trial Site Tempe Arizona United States 85281
    4 Clinical Trial Site Carlsbad California United States 92008
    5 Clinical Trial Site Garden Grove California United States 92844
    6 Clinical Trial Site Huntington Beach California United States 92647
    7 Clinical Trial Site La Mesa California United States 91942
    8 Clinical Trial Site Long Beach California United States 90806
    9 Clinical Trial Site Pomona California United States 91767
    10 Clinical Trial Site San Diego California United States 92103
    11 Clinical Trial Site Vista California United States 92083
    12 Clinical Trial Site Bradenton Florida United States 34208
    13 Clinical Trial Site Clearwater Florida United States 33756
    14 Clinical Trial Site Coral Gables Florida United States 33134
    15 Clinical Trial Site Inverness Florida United States 34452
    16 Clinical Trial Site Jacksonville Florida United States 32256
    17 Clinical Trial Site Miami Florida United States 33126
    18 Clinical Trial Site Naples Florida United States 34102
    19 Clinical Trial Site Orlando Florida United States 32162
    20 Clinical Trial Site Orlando Florida United States 32801
    21 Clinical Trial Site Pembroke Pines Florida United States 33027
    22 Clinical Trial Site Tampa Florida United States 33603
    23 Clinical Trial Site Winter Haven Florida United States 33880
    24 Clinical Trial Site Winter Park Florida United States 32789
    25 Clinical Trial Site Savannah Georgia United States 31406
    26 Clinical Trial Site Snellville Georgia United States 399978
    27 Clinical Trial Site Valparaiso Indiana United States 46383
    28 Clinical Trial Site Louisville Kentucky United States 40202
    29 Clinical Trial Site Lake Charles Louisiana United States 70601
    30 Clinical Trial Site New Orleans Louisiana United States 70769
    31 Clinical Trial Site Prairieville Louisiana United States 70769
    32 Clinical Trial Site Baltimore Maryland United States 21229
    33 Clinical Trial Site Jefferson City Missouri United States 65109
    34 Clinical Trial Site Saint Louis Missouri United States 63141
    35 Clinical Trial Site Henderson Nevada United States 89052
    36 Clinical Trial Site New York New York United States 10036
    37 Clinical Trial Site Greensboro North Carolina United States 27403
    38 Clinical Trial Site Greenville North Carolina United States 27834
    39 Clinical Trial Site Monroe North Carolina United States 28112
    40 Clinical Trial Site Marion Ohio United States 43302
    41 Clinical Trial Site Norman Oklahoma United States 73072
    42 Clinical Trial Site Medford Oregon United States 97504
    43 Clinical Trial Site Little River South Carolina United States 29566
    44 Clinical Trial Site Rock Hill South Carolina United States 29732
    45 Clinical Trial Site Memphis Tennessee United States 38119
    46 Clinical Trial Site New Tazewell Tennessee United States 37825
    47 Clinical Trial Site Amarillo Texas United States 79109
    48 Clinical Trial Site Cedar Park Texas United States 78613
    49 Clinical Trial Site Coppell Texas United States 75019
    50 Clinical Trial Site Dallas Texas United States 75224
    51 Clinical Trial Site Dallas Texas United States 75251
    52 Clinical Trial Site Sherman Texas United States 75092
    53 Clinical Trial Site Burke Virginia United States 22015
    54 Clinical Trial Site Puyallup Washington United States 98372
    55 Clinical Trial Site Kenosha Wisconsin United States 53142
    56 Clinical Trial Site Burlington Ontario Canada
    57 Clinical Trial Site Concord Ontario Canada
    58 Clinical Trial Site Etobicoke Ontario Canada
    59 Clinical Trial Site Toronto Ontario Canada
    60 Clinical Trial Site Winnipeg Ontario Canada
    61 Clinical Trial Site Chicoutimi Quebec Canada
    62 Clinical Trial Site Lévis Quebec Canada
    63 Clinical Trial Site Pointe-Claire Quebec Canada
    64 Clinical Trial Site Sherbrooke Quebec Canada
    65 Clinical Trial Site Trois-Rivières Quebec Canada
    66 Clinical Trial Site Victoriaville Quebec Canada
    67 Clinical Trial Site Québec Canada
    68 Clinical Trial Site Tallinn Estonia
    69 Clinical Trial Site Tallin Estonia
    70 Clinical Trial Site Tartu Estonia
    71 Clinical Trial Site Daugavpils Latvia
    72 Clinical Trial Site Kuldīga Latvia
    73 Clinical Trial Site Riga Latvia
    74 Clinical Trial Site Kaunas Lithuania
    75 Clinical Trial Site Panevėžys Lithuania
    76 Clinical Trial Site Vilnius Lithuania
    77 Clinical Trial Site Czestochowa Poland
    78 Clinical Trial Site Gdańsk Poland
    79 Clinical Trial Site Katowice Poland
    80 Clinical Trial Site Poznań Poland
    81 Clinical Trial Site Warszawa Poland
    82 Clinical Trial Site Wrocław Poland
    83 Clinical Trial Site Chelmsford United Kingdom
    84 Clinical Trial Site Dundee United Kingdom
    85 Clinical Trial Site Edinburgh United Kingdom
    86 Clinical Trial Site Fowey United Kingdom
    87 Clinical Trial Site Glasgow United Kingdom
    88 Clinical Trial Site Hexham United Kingdom
    89 Clinical Trial Site Liskeard United Kingdom
    90 Clinical Trial Site London United Kingdom
    91 Clinical Trial Site Newquay United Kingdom
    92 Clinical Trial Site Penzance United Kingdom
    93 Clinical Trial Site Plymouth United Kingdom
    94 Clinical Trial Site Torpoint United Kingdom

    Sponsors and Collaborators

    • Alnylam Pharmaceuticals

    Investigators

    • Study Director: Medical Director, Alnylam Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Alnylam Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT05103332
    Other Study ID Numbers:
    • ALN-AGT01-003
    • 2021-003776-13
    First Posted:
    Nov 2, 2021
    Last Update Posted:
    Aug 17, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Alnylam Pharmaceuticals
    High blood pressure
    Hypertension
    Hypertensive
    siRNA
    Angiotensinogen
    AGT
    Additional relevant MeSH terms:
    Hypertension
    Amlodipine
    Olmesartan
    Indapamide

    Study Results

    No Results Posted as of Aug 17, 2022